複素環式化合物の合成研究(第430報) : Camptothecin関連化合物の合成研究(第2報) : 4-Ethyl-4-hydroxy-5-methoxy-6-methyl-3-oxo-1,2,3,4-tetrahydro-2,7-naphthyridineの合成

抄録

In order to synthesize a compound having an E-ring of camptothecin, a Grignard reaction of 3-acetoxy-5-acetoxymethyl-4-cyano-2-methylpyridine (IX) with ethylmagnesium bromide was carried out and a mixture of a lactone (XI) and a lactam (XII) was obtained unexpectedly. The formation mechanism of these abnormal products was discussed. On the other hand, the reaction of 3-O-methyl-4-pyridoxic acid lactone with ethylmagnesium bromide gave 5-hydroxymethyl-3-methoxy-2-methyl-4-propionylpyridine (XVIII) in 48% yield as expected. However, the reaction of XVIII with hydrogen cyanide in hydrochloric acid gave a lactam (XIX), instead of a lactone (XX). Furthermore, the reaction of methyl 3-cyano-4-ethoxycarbonyl-1, 2-dihydro-2-oxo-6-pyridinecarboxylate (XXIV) with methyl acrylate under the above conditions gave XXVI instead of the desired compound (XXV).